{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T21:15:57Z","timestamp":1773695757043,"version":"3.50.1"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T00:00:00Z","timestamp":1599609600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T00:00:00Z","timestamp":1599609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Med"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>This study focused on the roles of lncRNA THRIL in coronary atherosclerotic heart disease (CAD) through regulating AKT signaling pathway and directly interacting with FUS.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>QRT-PCR was conducted to detect the expression of THRIL in CAD blood samples and endothelial progenitor cells (EPCs). Cell autophagy of EPCs was examined through Cyto-ID Autophagy Detection Kit. CCK-8 assay and flow cytometry were carried out to assess cell viability and apoptosis under various interference conditions. Western blotting was conducted to detect the expression of interest proteins. The expression levels of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were measured by qRT-PCR. The direct interactions between HCG18 and FUS was confirmed through RNA electrophoretic mobility shift assay (RNA EMSA) and RNA immunoprecipitation (RIP) assay.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>THRIL was upregulated in CAD blood samples and EPCs. Knockdown of THRIL in EPCs promoted cell viability, inhibited cell autophagy and further suppressed the development of CAD. Over-expression of THRIL induced inactivation of AKT pathway, while knockdown of THRIL played reversed effects. THRIL directly interacted with FUS protein and knockdown of FUS reversed the over-expressing effect of THRIL on cell proliferation, autophagy and the status of AKT pathway.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>THRIL inhibits the proliferation and mediates autophagy of endothelial progenitor cells via AKT pathway and FUS.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s10020-020-00201-2","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T14:32:10Z","timestamp":1599748330000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["THRIL mediates endothelial progenitor cells autophagy via AKT pathway and FUS"],"prefix":"10.1186","volume":"26","author":[{"given":"Jiandong","family":"Xiao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuli","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7640-7056","authenticated-orcid":false,"given":"Xinchun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,9,9]]},"reference":[{"issue":"1","key":"201_CR1","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/s10517-017-3753-7","volume":"163","author":"AA Ansheles","year":"2017","unstructured":"Ansheles AA, Rvacheva AV, Sergienko IV. Effect of atorvastatin therapy on the level of CD34(+)CD133(+)CD309(+) endothelial progenitor cells in patients with coronary heart disease. Bull Exp Biol Med. 2017;163(1):133\u20136.","journal-title":"Bull Exp Biol Med"},{"issue":"3","key":"201_CR2","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1210\/edrv-6-3-432","volume":"6","author":"C Becker","year":"1985","unstructured":"Becker C. Hypothyroidism and atherosclerotic heart disease: pathogenesis, medical management, and the role of coronary artery bypass surgery. Endocr Rev. 1985;6(3):432\u201340.","journal-title":"Endocr Rev"},{"issue":"4","key":"201_CR3","first-page":"564","volume":"20","author":"S Bitarafan","year":"2019","unstructured":"Bitarafan S, Yari M, Broumand MA, et al. Association of increased levels of lncRNA H19 in PBMCs with risk of coronary artery disease. Cell J (Yakhteh). 2019;20(4):564.","journal-title":"Cell J (Yakhteh)"},{"issue":"7","key":"201_CR4","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1038\/ncb2788","volume":"15","author":"P Boya","year":"2013","unstructured":"Boya P, Reggiori F, Codogno P. Emerging regulation and functions of autophagy. Nat Cell Biol. 2013;15(7):713\u201320.","journal-title":"Nat Cell Biol"},{"issue":"8","key":"201_CR5","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1093\/eurjhf\/hfr080","volume":"13","author":"AH Chaanine","year":"2011","unstructured":"Chaanine AH, Hajjar RJ. AKT signalling in the failing heart. Eur J Heart Fail. 2011;13(8):825\u20139.","journal-title":"Eur J Heart Fail"},{"issue":"3\u20136","key":"201_CR6","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/0921-8734(92)90021-G","volume":"275","author":"M Corral-Debrinski","year":"1992","unstructured":"Corral-Debrinski M, Shoffner J, Lott M, Wallace D. Association of mitochondrial DNA damage with aging and coronary atherosclerotic heart disease. Mutat Res. 1992;275(3\u20136):169\u201380.","journal-title":"Mutat Res"},{"issue":"7","key":"201_CR7","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/j.tcb.2017.01.001","volume":"27","author":"Z Deng","year":"2017","unstructured":"Deng Z, Purtell K, Lachance V, Wold MS, Chen S, Yue Z. Autophagy receptors and neurodegenerative diseases. Trends Cell Biol. 2017;27(7):491\u2013504.","journal-title":"Trends Cell Biol"},{"issue":"1\u20132","key":"201_CR8","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.mce.2010.04.022","volume":"325","author":"\u00d6 Erdogdu","year":"2010","unstructured":"Erdogdu \u00d6, Nathanson D, Sj\u00f6holm \u00c5, Nystr\u00f6m T, Zhang Q. Exendin-4 stimulates proliferation of human coronary artery endothelial cells through eNOS-, PKA-and PI3K\/Akt-dependent pathways and requires GLP-1 receptor. Mol Cell Endocrinol. 2010;325(1\u20132):26\u201335.","journal-title":"Mol Cell Endocrinol"},{"issue":"19","key":"201_CR9","doi-asserted-by":"publisher","first-page":"3550","DOI":"10.1111\/j.1742-4658.2011.08258.x","volume":"278","author":"FC Fiesel","year":"2011","unstructured":"Fiesel FC, Kahle PJ. TDP-43 and FUS\/TLS: cellular functions and implications for neurodegeneration. FEBS J. 2011;278(19):3550\u201368.","journal-title":"FEBS J"},{"issue":"6","key":"201_CR10","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1161\/01.CIR.101.6.660","volume":"101","author":"Y Fujio","year":"2000","unstructured":"Fujio Y, Nguyen T, Wencker D, Kitsis RN, Walsh K. Akt promotes survival of cardiomyocytes in vitro and protects against ischemia-reperfusion injury in mouse heart. Circulation. 2000;101(6):660\u20137.","journal-title":"Circulation."},{"issue":"1","key":"201_CR11","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1186\/s12967-016-0926-5","volume":"14","author":"S Greco","year":"2016","unstructured":"Greco S, Zaccagnini G, Perfetti A, et al. Long noncoding RNA dysregulation in ischemic heart failure. J Transl Med. 2016;14(1):183.","journal-title":"J Transl Med"},{"issue":"10","key":"201_CR12","doi-asserted-by":"publisher","first-page":"5062","DOI":"10.1111\/jcmm.13790","volume":"22","author":"F Guo","year":"2018","unstructured":"Guo F, Tang C, Li Y, et al. The interplay of Lnc RNA ANRIL and miR-181b on the inflammation-relevant coronary artery disease through mediating NF-\u03baB signalling pathway. J Cell Mol Med. 2018;22(10):5062\u201375.","journal-title":"J Cell Mol Med"},{"issue":"3","key":"201_CR13","first-page":"H699","volume":"299","author":"D Hamamdzic","year":"2010","unstructured":"Hamamdzic D, Fenning RS, Patel D, et al. Akt pathway is hypoactivated by synergistic actions of diabetes mellitus and hypercholesterolemia resulting in advanced coronary artery disease. Am J Phys Heart Circ Phys. 2010;299(3):H699\u2013706.","journal-title":"Am J Phys Heart Circ Phys"},{"key":"201_CR14","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s12950-019-0212-4","volume":"16","author":"M Hassanpour","year":"2019","unstructured":"Hassanpour M, Rahbarghazi R, Nouri M, Aghamohammadzadeh N, Safaei N, Ahmadi M. Role of autophagy in atherosclerosis: foe or friend? J Inflamm (Lond). 2019;16:8.","journal-title":"J Inflamm (Lond)"},{"issue":"1","key":"201_CR15","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1186\/s13287-020-01656-0","volume":"11","author":"M Hassanpour","year":"2020","unstructured":"Hassanpour M, Rezaie J, Darabi M, Hiradfar A, Rahbarghazi R, Nouri M. Autophagy modulation altered differentiation capacity of CD146(+) cells toward endothelial cells, pericytes, and cardiomyocytes. Stem Cell Res Ther. 2020;11(1):139.","journal-title":"Stem Cell Res Ther"},{"issue":"10","key":"201_CR16","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1016\/j.cellsig.2011.05.004","volume":"23","author":"I Hers","year":"2011","unstructured":"Hers I, Vincent EE, Tavar\u00e9 JM. Akt signalling in health and disease. Cell Signal. 2011;23(10):1515\u201327.","journal-title":"Cell Signal"},{"key":"201_CR17","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.yjmcc.2015.07.019","volume":"86","author":"M Ikutomi","year":"2015","unstructured":"Ikutomi M, Sahara M, Nakajima T, et al. Diverse contribution of bone marrow-derived late-outgrowth endothelial progenitor cells to vascular repair under pulmonary arterial hypertension and arterial neointimal formation. J Mol Cell Cardiol. 2015;86:121\u201335.","journal-title":"J Mol Cell Cardiol"},{"issue":"2","key":"201_CR18","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/0021-9150(75)90001-5","volume":"22","author":"A Keys","year":"1975","unstructured":"Keys A. Coronary heart disease\u2014the global picture. Atherosclerosis. 1975;22(2):149\u201392.","journal-title":"Atherosclerosis."},{"issue":"11","key":"201_CR19","doi-asserted-by":"publisher","first-page":"26797","DOI":"10.3390\/ijms161125990","volume":"16","author":"Y Kiriyama","year":"2015","unstructured":"Kiriyama Y, Nochi H. The function of autophagy in neurodegenerative diseases. Int J Mol Sci. 2015;16(11):26797\u2013812.","journal-title":"Int J Mol Sci"},{"issue":"9","key":"201_CR20","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1093\/eurheartj\/ehs043","volume":"33","author":"R Kumarswamy","year":"2012","unstructured":"Kumarswamy R, Lyon AR, Volkmann I, et al. SERCA2a gene therapy restores microRNA-1 expression in heart failure via an Akt\/FoxO3A-dependent pathway. Eur Heart J. 2012;33(9):1067\u201375.","journal-title":"Eur Heart J"},{"key":"201_CR21","doi-asserted-by":"publisher","first-page":"e40811","DOI":"10.7554\/eLife.40811","volume":"8","author":"S-C Ling","year":"2019","unstructured":"Ling S-C, Dastidar SG, Tokunaga S, et al. Overriding FUS autoregulation in mice triggers gain-of-toxic dysfunctions in RNA metabolism and autophagy-lysosome axis. Elife. 2019;8:e40811.","journal-title":"Elife."},{"issue":"2","key":"201_CR22","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.stemcr.2017.12.018","volume":"10","author":"L Marrone","year":"2018","unstructured":"Marrone L, Poser I, Casci I, et al. Isogenic FUS-eGFP iPSC reporter lines enable quantification of FUS stress granule pathology that is rescued by drugs inducing autophagy. Stem Cell Rep. 2018;10(2):375\u201389.","journal-title":"Stem Cell Rep"},{"issue":"1","key":"201_CR23","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/cdd.2008.163","volume":"16","author":"K Nishida","year":"2009","unstructured":"Nishida K, Kyoi S, Yamaguchi O, Sadoshima J, Otsu K. The role of autophagy in the heart. Cell Death Differ. 2009;16(1):31.","journal-title":"Cell Death Differ"},{"issue":"8708","key":"201_CR24","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/0140-6736(90)91656-U","volume":"336","author":"D Ornish","year":"1990","unstructured":"Ornish D, Brown SE, Billings J, et al. Can lifestyle changes reverse coronary heart disease?: The lifestyle heart trial. Lancet. 1990;336(8708):129\u201333.","journal-title":"Lancet"},{"issue":"11","key":"201_CR25","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.1080\/15548627.2018.1501132","volume":"14","author":"Y Osonoi","year":"2018","unstructured":"Osonoi Y, Mita T, Azuma K, et al. Defective autophagy in vascular smooth muscle cells enhances cell death and atherosclerosis. Autophagy. 2018;14(11):1991\u20132006.","journal-title":"Autophagy."},{"issue":"1","key":"201_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/onc.2015.99","volume":"35","author":"VW Rebecca","year":"2016","unstructured":"Rebecca VW, Amaravadi RK. Emerging strategies to effectively target autophagy in cancer. Oncogene. 2016;35(1):1\u201311.","journal-title":"Oncogene."},{"issue":"12","key":"201_CR27","doi-asserted-by":"publisher","first-page":"2822","DOI":"10.1016\/j.neurobiolaging.2014.07.026","volume":"35","author":"H-H Ryu","year":"2014","unstructured":"Ryu H-H, Jun M-H, Min K-J, et al. Autophagy regulates amyotrophic lateral sclerosis-linked fused in sarcoma-positive stress granules in neurons. Neurobiol Aging. 2014;35(12):2822\u201331.","journal-title":"Neurobiol Aging"},{"issue":"1","key":"201_CR28","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s12944-018-0728-2","volume":"17","author":"G Wang","year":"2018","unstructured":"Wang G, Li Y, Peng Y, Tang J, Li H. Association of polymorphisms in MALAT1 with risk of coronary atherosclerotic heart disease in a Chinese population. Lipids Health Dis. 2018;17(1):75.","journal-title":"Lipids Health Dis"},{"issue":"5","key":"201_CR29","doi-asserted-by":"publisher","first-page":"564","DOI":"10.5603\/CJ.a2018.0054","volume":"26","author":"J Xia","year":"2019","unstructured":"Xia J, Jiang N, Li Y, Wei Y, Zhang X. The long noncoding RNA THRIL knockdown protects hypoxia-induced injuries of H9C2 cells through regulating miR-99a. Cardiol J. 2019;26(5):564\u201374.","journal-title":"Cardiol J"},{"issue":"12","key":"201_CR30","doi-asserted-by":"publisher","first-page":"2223","DOI":"10.4161\/15548627.2014.981789","volume":"10","author":"Y Xiong","year":"2014","unstructured":"Xiong Y, Yepuri G, Forbiteh M, et al. ARG2 impairs endothelial autophagy through regulation of MTOR and PRKAA\/AMPK signaling in advanced atherosclerosis. Autophagy. 2014;10(12):2223\u201338.","journal-title":"Autophagy."},{"issue":"9","key":"201_CR31","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1161\/CIRCRESAHA.108.171488","volume":"102","author":"Q Xu","year":"2008","unstructured":"Xu Q. Stem cells and transplant arteriosclerosis. Circ Res. 2008;102(9):1011\u201324.","journal-title":"Circ Res"},{"issue":"11","key":"201_CR32","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1016\/j.bbagrm.2014.08.012","volume":"1839","author":"G Yang","year":"2014","unstructured":"Yang G, Lu X, Yuan L. LncRNA: a link between RNA and cancer. Biochim Biophys Acta. 2014;1839(11):1097\u2013109.","journal-title":"Biochim Biophys Acta"},{"issue":"3","key":"201_CR33","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1097\/MOH.0000000000000041","volume":"21","author":"M Zhang","year":"2014","unstructured":"Zhang M, Malik AB, Rehman J. Endothelial progenitor cells and vascular repair. Curr Opin Hematol. 2014;21(3):224\u20138.","journal-title":"Curr Opin Hematol"},{"issue":"1","key":"201_CR34","doi-asserted-by":"publisher","first-page":"7491","DOI":"10.1038\/s41598-017-07611-z","volume":"7","author":"Z Zhang","year":"2017","unstructured":"Zhang Z, Gao W, Long Q-Q, et al. Increased plasma levels of lncRNA H19 and LIPCAR are associated with increased risk of coronary artery disease in a Chinese population. Sci Rep. 2017;7(1):7491.","journal-title":"Sci Rep"},{"issue":"4","key":"201_CR35","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.18632\/aging.101766","volume":"11","author":"Y Zhu","year":"2019","unstructured":"Zhu Y, Yang T, Duan J, Mu N, Zhang T. MALAT1\/miR-15b-5p\/MAPK1 mediates endothelial progenitor cells autophagy and affects coronary atherosclerotic heart disease via mTOR signaling pathway. Aging-Us. 2019;11(4):1089\u2013109.","journal-title":"Aging-Us."}],"container-title":["Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10020-020-00201-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s10020-020-00201-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10020-020-00201-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T23:29:55Z","timestamp":1631143795000},"score":1,"resource":{"primary":{"URL":"https:\/\/molmed.biomedcentral.com\/articles\/10.1186\/s10020-020-00201-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,9]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["201"],"URL":"https:\/\/doi.org\/10.1186\/s10020-020-00201-2","relation":{},"ISSN":["1076-1551","1528-3658"],"issn-type":[{"value":"1076-1551","type":"print"},{"value":"1528-3658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,9]]},"assertion":[{"value":"18 December 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 September 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The present study was approved by the Ethics Committee of Beijing Chaoyang Hospital. The research has been carried out in accordance with the World Medical Association Declaration of Helsinki. All patients and healthy volunteers provided written informed consent prior to their inclusion within the study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"86"}}